HU201651B - Process for producing substituted pyrimidines and insecticid and acaricid media containing same as agents - Google Patents

Description

The novel compounds of the present invention are compounds of the formula I and their salts wherein

R 1 is hydrogen or C 1-6 alkyl,

R _{2 is} hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 2-6 alkenyl or C 2-6 alkynyl, or R 1 and R _{2 taken} together form - (CH ₂ ) ₄ - or - (CH ₂ ) _A group of ₅ ,

R _{3 is} hydrogen or a group -CO-R ₅ ,

R ₄ is -NH ₂ , -NH-CO-R 5,

R ₇ R ¹¹ / -N = CN <

or -NH-CH = NR ₁₀

R 40

R 1 is C 1 -C 10 alkyl or perhalogenated C 1 -C 3 alkyl,

R _{7 is} hydrogen,

R ₈ and R ₉ are each independently hydrogen

C 1 -C 3 alkyl;

R 10 is -SO ₂ - (C 1 -C 4) alkyl or

X OR ₁₄ -P <

group 50;

Y Ru

R _I4 and _R15 are independently C1-5alkyl 55

X and Y are independently oxygen or sulfur.

Halogen atoms or halogen substituents in the context of the present invention include fluorine, chlorine, bromine or iodine, preferably fluorine and chlorine. 60

Due to their advantageous properties, compounds of general formula (I) in which R, hydrogen or C1-C4 alkyl,

R _{2 is C} 1-4 alkyl or C 3-6 cycloalkyl, or R 1 and R _{2 taken} together form - (CRX- or - (CH ₂ ) ₅ ) -

R _{3 is} hydrogen,

R ₄ is -NH ₂ or -NH-CO-R _S , cs

R _{5 is C} 1-4 alkyl or perhalogenated C 1-3 alkyl;

salts of such compounds as well as compounds of formula I wherein R, hydrogen, methyl or ethyl are also important,

R _{2 is C} 1-4 alkyl or cyclopropyl,

R _{3 is} hydrogen,

R _{4 is} a pipe powder of the formula -NH ₂ or -NH-CO-R ₅ ,

_R5 is C1-3 alkyl, and salts of such compounds are preferred.

In view of their potent pest control activity, the compounds of formula I and their salts are particularly preferred in which

R, hydrogen, methyl or ethyl,

R _{2 is} cyclopropyl,

R _{3 is} hydrogen and

R 1 is -NH ₂ or -NH-CO-C ₂ H ₅ Salts of compounds of formula I are meant to include physiologically tolerable addition salts of inorganic and organic acids. Examples of inorganic acids are hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, phosphoric acid, nitric acid. Organic acids include trifluoroacetic acid, trichloroacetic acid, formic acid, oxalic acid, succinic acid, maleic acid, lactic acid, glycolic acid, aconitic acid, citric acid, benzoic acid, benzenesulfonic acid, methanesulfonic acid.

The compounds of formula (I) may be prepared by:

(a) a compound of formula (II) with ammonia; or

b) reacting the compound of formula (III) with an amine of formula (IV), and the resulting compound of formula (I) wherein R _{3 is} hydrogen and R 1 is -NH ₂ , optionally in a manner known per se; (I) is converted to the aimed compound wherein R ₃ -CO-R ₅ group of the formula and / or R, -NH-CO-R _s,

obsession

R ₉

-NH-CH = NR ₁₀

Wherein R _{b is} R ₂ , R _3i, R ₄ , R 5, R 6, R 7, R 8, R 9, R 10. R ₄ , R ₈ > X and Y are as defined above, and n is an integer of 0.1 or 2, and a resulting compound of formula (I) is converted into a salt thereof.

In the above process variant (a), a sulfonyl compound of formula II (n = 2) is reacted with ammonia, usually at a temperature between 10 'C and 100' C, in an organic solvent such as acetonitrile, tetrahydrofuran, dioxane or solvent-water. Similar reaction conditions apply to process variant b) when 2-chloro-4,6-diamino-5-cyanopyrimidine (III) is reacted with an amine (IV). When the methylthio compound of formula II (n = O) is reacted as a starting material in process variant a), it is preferably reacted with ammonia in an autoclave at elevated pressure at a temperature between 100 ° C and 170 ° C, most preferably about 160 ° C. you.

Said conversion of a compound of formula (I) wherein R _{4 is} -NH ₂ into a compound of formula (I) wherein 1¾ of another meaning given in the present invention may be accomplished by positioning the amino group at the 6-position of the pyrimidine ring with suitable reaction partners known per se. For example, (I), 6-aminopyrimidine of the formula _{Hal-CO-R5, Hal-SO2} -R <j, (R5 CO) ₂ O or R by reaction with ₆ 0-CH = N-Rio type compounds,

In the 6-position, the appropriately substituted compounds of formula (I) are obtained wherein Hal is halogen, preferably chlorine and R 1, R ₆ and R ₁₀ are as defined above. If a compound of formula I is to be prepared wherein R ₄ is

R-7

-N = CN ζ, for example, 6-NH _{2 is} one

Acctal of formula CN \ - where r is ₆ or ₉

R ₆ , R ₇ , R ₈ and R are as defined above. In a similar manner and using a suitable reaction partner, the 4-aminopyrimidines of formula (I) wherein R _{3 is} hydrogen may be prepared from compounds of formula (I) wherein R ₃ is -CO-R ₅ or -SO ₂ -R 6 represents a group of the formula. The acylation described above is carried out at normal pressure in an inert solvent or diluent in the presence of a base at 0 to 120 ° C, preferably at 40 to 80 ° C. Examples of solvents and diluents include:

Alkanes, such as n-pentane, and homologues thereof, including isomers, to n-heptadecane; ethers such as diethyl ether, dipropyl ether, dibutyl ether, dimethoxyethane, dioxane or tetrahydrofuran; chlorinated hydrocarbons such as chloroform, methylene chloride, carbon tetrachloride or chlorobenzene; aromatic hydrocarbons such as benzene, toluene or xylene. In addition, additional inert solvents and diluents may be used in the processes. Suitable bases for use in these processes include, for example, alkylamines, such as triethylamine or diisopropylethylamine, and pyridine or N-methylpyrrolidone.

The starting compounds of formula II are novel. These compounds can be prepared as follows:

a) Compounds of formula II in which n is 0, for example according to Scheme A.

The N-cyano-dithiocarbonimidic acid dimethyl ester of formula (V) used as starting material in this process and the salt of formula (VI) formed by reaction with malononitrile are known (See, Trav. Ch. 90, 1971, 463; J. Chem. Soc., Chem. Comm. 1974,350) Ring closure of the salt of Formula VI with 5N hydrochloric acid followed by reaction of the resulting pyrimidine of Formula VII with a corresponding amine of Formula IV affords a compound of Formula II. where n = 0.

b) Compounds of formula II wherein n is 0 may also be prepared according to Scheme B.

The sodium salt of the urea of formula (IX) and the uracil of formula (X) in this scheme are known (see J. Chem. Soc., Chem. Comm. 1974, 350; Hclv. Chim. Act. 1985, 1155). . The novel substituted pyrimidines of formulas XI and XII are prepared in a manner known per se. Reaction of compound (XII) with ammonia gives compound (II) where n = 0.

c) Starting materials of formula II wherein n is 1 or 2 can be prepared by oxidation of compounds of formula II wherein n = 0 in a manner known per se (see "The Chemistry of Heterocyclic Compounds", vol. 16). Pyrimidinck, Intersc. Publ. Inc., NY, 1959).

The starting compound of formula (III), i.e., 2-chloro-4,6-diamino-5-cyanopyrimidine, is described in Chem. 1968.1244 ref known, but according to the Scheme C of the above sulfone compound (VII) is oxidized, and the _{-SO2 CH3} group is replaced with ammonia _-NH2 groups can be prepared.

Insecticidal 2,4,6-liamino-5-nitropyrimidines, the amino groups of which may be optionally substituted, are already known from European Patent Application 0 084 758. The structural difference between the known compounds and the active compounds of formula I according to the invention is essentially the cyano group in the 5-position.

Surprisingly, it has been found that the compounds of the formula I according to the invention and their salts exhibit very good insecticidal activity and in addition are non-harmful to plants and have very low warm-blood toxicity. Thus, they are particularly suitable for controlling insects on plants and animals and representatives of the genus Acarina.

The compounds of formula (I) are particularly useful for controlling insects of the following orders: Lepidoptera, Colcoptera, Homoptera, Heteroptera, Diptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, and Psocoptcra, of the genera Ixodidae, Argasidae, Tetranychidae and Dermanysidae.

Flies such as Musca domestica and mosquitoes3

In addition to their action against larvae, the active compounds of the present invention are also useful for chewing insects on ornamental crops, especially cotton crops, such as Spodoptera littoralis and Heliothis virescens, and for chewing insects in orchards and vegetable plants, also to control varivestis. In addition, the compounds of formula I are very effective against rice pests. In addition, the compounds of formula I exhibit a very good larvicidal activity against insects, in particular chewing larvae. When the active compounds of the present invention are consumed by pests with food during the adult insect stage, in many cases, especially in Colleoptera species, such as Anthonomus grandis, oviposition and / or pupation are significantly restricted.

In addition, the compounds of formula (I) can be used very well in domestic and farm animals against ectoparasites such as Lucilia sericata, for example in the treatment of animals, barns and feed. When treated with the active compounds of the present invention in grazing animals, such as by bovine bathing, watering or spraying, the active compounds of the invention exhibit a surprising adhesion effect and exhibit a very long duration of toxicity on the skin or hair of the animals. Examples of such ectoparasites are the harmful Diptera species. In this way, prematurely washing or washing off the active ingredient on the livestock surface by rain.

A particular advantage of the compositions comprising the active ingredient of the invention is that it can be administered orally to farm animals; in particular, the active compounds exhibit ex post and prolonged insecticidal activity in faecal secretion from the digestive tract. Thus, infection with harmful insects, especially Diptera species, can be prevented as soon as pests appear in the animal environment, such as stables, passages and pastures, as Diptera larvae, which develop from laying eggs, are instantly killed. Particularly important in this particular application is the fact that the compounds of the present invention are physiologically inactive because of their structural properties. This targeted method of controlling insect multiplication is significantly more efficient and at the same time more economical than conventional large surface disinfection methods for stables and walkways.

The compounds of formula (I) show good insecticidal activity in that the pests in question are killed by at least 50-60%.

The activity of the compounds of the present invention and of the compositions containing them as active ingredients can be substantially enhanced by the addition of other insecticides and / or acaricides and adapted to the particular circumstances. Examples of such additives include organophosphorus compounds, nitrophenols and their derivatives, formamidine derivatives, ureas, carbamate derivatives, pyrethroids, chlorinated hydrocarbons and Bacillus thuringiensis preparations.

The compounds of the present invention are preferably used in conjunction with excipients commonly used in formulation techniques, and may be formulated, for example, in the following formulations: concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, encapsulated substances. The method of application is, for example, spraying, fogging, dusting or irrigation, depending on the agent available, the purpose to be achieved and the particular circumstances.

Compositions comprising the active ingredient of formula (I) and other insecticidal or acaricidal active ingredient and optionally a solid or liquid additive may be prepared by methods known per se, for example by adding the active ingredient to excipients such as solvents, solid carriers and optionally surfactant compounds (tcnzidckkcl) are thoroughly mixed and / or rubbed.

Suitable solvents include: aromatic hydrocarbons, especially C8-C12 fractions, such as xylene mixtures or substituted naphthalenes, phthalic acid derivatives such as dibutyl or dioctylphalate, aliphatic hydrocarbons such as cyclohexanes, paraffins, alcohols, ethers and esters such as ethanol, ethylene glycol, ethylene glycol monomethyl or ethyl ester, ketones such as cyclohexanone, highly polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, and optionally cpoxidized oil, for example, epoxidized coconut oil or soybean oil or water.

Solid carriers, for example, in the preparation of dusts and dispersible powders, are generally natural rocky meals such as chelate, talc, kaolin, montmorrillonite or attapulgite. Highly dispersed silica or highly dispersed absorbent polymers may be added to improve physical properties. As granular, adsorptive granule carriers, porous types such as limestone, brick rubble, sepiolite, or entonite are used, while non-sorptive carriers include chelate or sand. In addition, many inorganic or organic granular materials such as dolomite or apirote plant residues can be used.

Depending on the nature of the material to be formulated or the combination of these agents with other insecticides or acaricides, nonionic cationic and / or anionic surfactants which are highly emulsifiable, dispersing and wetting agents are suitable as surfactants. Tensides include tensideslack.

So-called water-soluble soaps as well as water-soluble synthetic surfactants are suitable as anionic surfactants.

As soaps, the alkali metal, alkaline earth metal, or optionally substituted ammonium salts of higher fatty acids (C 10 -C 22) or optionally substituted ammonium salts of natural or stearic acid or mixtures of natural fatty acids such as coconut oil or tallow oil are suitable. Further, surfactants include fatty acid methyl taurine salts and modified and unmodified phospholipids.

However, so-called synthetic surfactants, mainly fatty sulfonates, fatty sulfates,

EN 201 651 Β sulphonated benzimidazole derivatives or alkylaryl sulphonates are used.

Fatty sulfonates or sulfates usually exist in the form of their alkali metal, alkaline earth metal or optionally substituted ammonium salts and generally contain a C 8 -C 22 alkyl group, in which case the alkyl group includes the alkyl portion of the acyl group, such as lignin sulfonic acid, or sodium or calcium salts of fatty alcohol sulphate mixtures obtained from natural fatty acids. Also included are the salts of sulfonic acids of sulfuric esters and fatty alcohol ethylene oxide adducts.

The sulfonated benzimidazole derivatives preferably contain two sulfonic acid groups and a fatty acid group of about 8 to about 22 carbon atoms. Examples of alkylaryl sulfonates are the sodium, calcium or triethanolamine salts of dodecyl bis-benzenesulfonic acid, dibutylnaphthalenesulfonic acid or a formaldehyde of a naphthalenesulfonic acid formaldehyde. Also included are the salts of the corresponding phosphates, such as the phosphoric acid ester of a p-nonylphenol (4-14) -ctylene oxide adduct.

Nonionic surfactants include, in particular, aliphatic or cycloaliphatic alcohols, saturated or unsaturated fatty acids and alkylphenols with polyglycol ether derivatives which may contain from 3 to 30 glycol ethers and from 8 to 20 carbon atoms in the (aliphatic) hydrocarbon group and alkyl moieties from 6 to 6 carbon atoms. Suitable nonionic surfactants are also water-soluble polypropylene glycol polyethylene oxide adducts having 20 to 250 ethylene glycol ether groups and 10 to 100 propylene glycol ether groups, ethylene diaminopolypropylene glycols, and alkyl polyols containing from 1 to 10 carbon atoms in the alkyl chain. These compounds generally contain from 1 to 5 ethylene glycol units per propylene glycol unit.

Non-ionic surfactants include nonylphenol polyethoxyethanols, castor oil polyglycol ethers, polypropylene polyethylene oxide adducts, tributyl phenoxy polyethoxyethanol, polyethylene glycol and octylphenoxy polytoxyethanol. Fatty acid esters of polyoxyethylene sorbitan such as polyoxyethylene sorbitan trioleate are also contemplated.

Cationic surfactants include, in particular, quaternary ammonium salts which contain at least one C 8 -C 22 alkyl group as the N-substituent and a further optionally lower alkyl optionally halogenated, benzyl or lower hydroxyalkyl group. The salts are preferably halides, methyl sulfates or ethyl sulfates, such as stearyl trimethyl ammonium chloride or benzyl di- (2-chloroethyl) ethyl ammonium bromide.

Tensides used in formulation techniques are described, inter alia, in the following literature:

Mc Cutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, New Jersey, 1979;

Dr. Helmut Stache: TensidTaschenbuch, Carl Hanser Verlag, Munich / Wien, 1981.

Insecticidal compositions generally contain from 0.1 to 95% by weight of the active ingredient of the present invention, from 0.01 to 95% by weight of a solid or liquid carrier or excipient and from 0 to 25%, in particular from 0.1 to 20% by weight, of surfactant.

While commercial products are more concentrated agents, the end user will typically use diluted formulations with substantially lower concentrations of the active ingredient.

The agents may contain additional additives, such as stabilizers, antifoams, viscosity regulators, binders, preservatives, and nutrients, or other active ingredients to achieve a specific effect.

Example 1

a) Preparation of 2-cyclopropylamino-4-amino-5-cyano-6-methylthiopyrimidine (starting material)

i) To a solution of 2-cyano-3-cyano-amino-3-methylthioacrylonitrile sodium salt (93 g) in water (425 ml) was added dropwise 650 ml of concentrated hydrochloric acid while cooling with ice water. The reaction mixture is then stirred for about 12 hours at room temperature. The resulting precipitate was filtered and treated with aqueous sodium carbonate solution. 20 g of the resultant 2-chloro-4-amino-5-cyano-6-methylthiopyrimidine (m.p. 268 ° C) are suspended in 250 ml of aedetonitrile and 11.4 g of cyclopropylamine are stirred at reflux under vigorous stirring. dropwise. The reaction mixture is then stirred for about 12 hours and water is added. The precipitate formed is filtered off. The title compound (XIV) is obtained (Compound 3.1), m.p. 215-218 ° C.

ii) To a mixture of 18.3 g of 5-cyano-6-methylthiouracil and 80 ml of phosphorus oxychloride is slowly added 20 g of Ν, Ν-diethylaniline. The reaction mixture was refluxed for 1.5 hours and then concentrated. To the residue was added 200 ml of ice water, stirred, filtered and washed with water. After drying, the crude product is chromatographed on silica gel (eluent: toluene-chloroform-acetic acid 6: 3: 1). 22 g of the thus obtained 2,4-dichloro-5-cyano-6-methylthiopyrimidine (m.p. 118-120 ° C) are dissolved in 200 ml of acetonitrile and at -10 ° C a solution of 11.4 g of cyclopropylamine in 40 ml of acetonitrile is obtained. drip it. The reaction mixture was stirred for 2 hours at room temperature and then poured into 2 liters of ice water. The resulting residue was filtered. 16.1 g of the thus obtained 2-cyclopropylamino-4-chloro-5-cyano-6-methylthiopyrimidine (m.p. 139-142 'C) (XV) are mixed with 100 ml of acetonitrile. To the resulting slurry was poured 300 ml of 30% aqueous ammonia solution and stirred for 10 hours at room temperature and then for 5 hours under reflux. The reaction mixture was cooled, and the resulting solid residue was filtered and washed with water. Recrystallization from 150 ml of methylcellosolve affords the title compound of the formula (i), m.p. 215-218 ° C.

b) Preparation of 2-Cyclopropyl-amino-4,6-diamino-5-cyanopyrimidine

33.7 g of 2-cyclopropylamino-4-amino-5-cyano-6-methylthiopyrimidine (a) prepared as described in a) are treated with 150 g of ammonia in an autoclave at 150 ° C for 15-20 hours. The resulting reaction product was stirred several times with water and then filtered. In this way, the title compound of formula (XVI) (compound 1.1), m.p. 249-251 'C, is obtained.

Example 2

a) Preparation of 2-diethylamino-4-amino-5-cyano-6-methylsulfonylpyrimidine (starting material)

47.5 g of 2-diethylamino-4-amino-5-cyano-6-methylthio5

HU 201 651 Β

Pyrimidine was added to 650 ml of methylene chloride and, without cooling, 88.7 g of 3-chloroperbenzoic acid were added. The reaction mixture was stirred for 2 hours and then filtered. The filtrate was evaporated and the residue was slurried with diethyl ether and filtered. There is thus obtained the title compound (XVII) (compound 3.2), m.p. 170-172 ° C.

b) Preparation of 2-diethylamino-4,6-diamino-5-cyanopyrimidine

To a mixture of 300 ml of 30% aqueous ammonia and 100 ml of acetonitrile was added 26.9 g of 2-diethylamino-4-amino-5-cyano-6-methylsulfonylpyrimidine (26.9 g) at room temperature. The reaction mixture is refluxed for about 12 hours, cooled and the precipitate formed is filtered off. It is then treated with water and filtered. The title compound (XVIII) m.p. 222-224'C (compound 1.2) is obtained.

Example 3

Preparation of 2-diethylamino-4-armno-5-cyano-6-isobutyrylamino-pyrimidine

To a solution of 10.3 g of 2-diethylamino-4,6-diamino-5-cyanopyrimidine (prepared as in Example 2) in 90 ml of tetrahydrofuran is added 7 g of triethylamine. To this solution was added dropwise 8.5 g of isobutyric anhydride at 60 ° C. The reaction mixture was refluxed for 48 hours, concentrated and the resulting residue was washed with diethyl ether. The title compound (XIX), m.p. 151-152 ° C (compound 1.3) is obtained.

Example 4

Preparation of N, Ν-Dimethyl-N '- (2-cyanopropylamino-4-amino-5-cyanopyrimidinyl-6) -formamidine

Of a solution of 3.8 g of 2-cyclopropylamino-4,6-diamino-5-cyanopyrimidine in 100 ml of dioxane at 45-50 ° C

3.7 g of dimethylformamide diethyl acetate are added dropwise. The reaction mixture was stirred for 8 hours at 45-50 ° C. After distilling off the solvent, the crude product is recrystallized from ethanol to give the title compound XX, m.p. 192-195 ° C (compound 1.4).

Example 5:

Preparation of 2-chloro-4,6-diamino-5-cyanopyrimidine (starting material) A suspension of g of finely powdered 2-chloro-4-amino-5-cyano-6-methylthiopyrimidine in 750 ml of dioxane and 250 ml of water was prepared. Cool to 0 ° C. A strong stream of chlorine gas is then introduced into this suspension with stirring and without cooling. After about 20 minutes, a clear solution was obtained. After a further 30 minutes, the introduction of chlorine gas was complete and the reaction mixture was stirred for 1.2 hours.

The reaction mixture was concentrated and the residue was slurried with 600 ml of ice water and filtered. The 2-chloro-4-amino-5-cyano-6-methylsulfonylpyrimidine (m.p. 253 DEG C. decomposition) was obtained as a gray solid with 25 g of 30% aqueous ammonia and 1000 ml of acetonitrile. stirring at room temperature for 1 hour. The reaction mixture was concentrated and the residue was slurried with water and filtered.

There is thus obtained the title compound (III), which melts at a temperature above 260 ° C (compound 5.1).

The following compounds of formula (I) are also prepared by the methods described above:

Compound number Ltd. R2 r ₃ R ₄ melting point (° C) 1.5 H -C ₃ H ₇ (i) H -nh ₂ 230-232 1.6 H -CHíCftj ^ Hs H -nh ₂ 195-197 1.7 -CH ₃ -CH ₃ H NH2 > 260 1.8 -C ₃ H ₇ (n) ~ C ₃ H ₇ (n) H -nh ₂ 204-206 1.9 -C ₄ H ₉ (n) -C ₄ H ₉ (n) H -nh ₂ 182-185 1:10 -CH ₃ C2H5 H -nh ₂ 250-251 1:11 - (CH ₂ ) 4 H -nh ₂ > 260 1:12 - (CH ₂ ) 5 H -nh ₂ 234-236 1:13 H -C (CH ₃ ) ₃ H -nh ₂ 180-183 1:14 -CH ₃ -C ₄ H ₉ (n) H NH2 194-196 1:15 H cyclopropyl H -NH-CO-CH (CH ₃ ) 2 215-218 1:16 H cyclopropyl H -NH-CO-C2H5 180-181 1:17 H cyclopropyl H -NH-CO-CH ₃ 203-205 1:18 C2H5 C2H5 H -NH-CO-C2H5 158-160 1:19 C2H5 C2H5 H -NH-CO-C (CH ₃ ) ₃ 113-115 1:20 C2H5 C2H5 H -nh-co-ch ₃ 168-171 1:21 C2H5 C2H5 H -NH-CO-C ₃ H ₇ (n) 149-150 1:22 H cyclopropyl H -NH-CO-C (CH ₃ ) ₃ 110-113 1:23 C2H5 C2H5 H -NH-CO-C ₄ H ₉ (n) 119-120 1:24 H cyclopropyl H -NH-CO-C ₃ H ₇ (n) 175-176 1:25 H cyclopropyl H -NH-CO-C ₄ H ₉ (n) 187-188 1:26 C2H5 C2H5 H -NH-CO-CF ₃ 190-191 1:27 H cyclopropyl H -NH-CO-CF ₃ 268 1:28 CH3 -C ₄ H ₉ (n) H -NH-CO-CH (CH ₃ ) ₂ 139-140 1:29 -ch ₃ C2H5 H -NH-CO-CH (CH ₃ ) 2 146-149 1:30 H cyclopropyl H -NH-CO-CH (C ₂ H ₅ ) ₂ 196-197

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EN 201 651 Β continued

Compound number Ri RZ R3 R4 melting point (° C) 1:31 C2H5 C2H5 H -NH-CO- (CH2) 4CH3 133-135 1:32 H cyclopropyl H -NH-CO- (CH2) 4CH3 170-173 1:33 H cyclopropyl H CH 3 1 -N = CH-N-CH ₃ 192-195

CH3

I

1:34 C2H5 C2H5 H -N = CH-N-CH ₃ 160-165 1:35 H cyclopropyl H -N = CH-NH-SO ₂ CH ₃ 203-205 1:36 C2H5 C2H5 H -N = CH-NH-SO2CH3 0 OC2H5 11 / 182-185 1:37 C2H5 C2H5 H -N = CH-NH-P ^ SC ₃ H ₇ (n) 127-128 1:38 -CH ₃ -CH ₂ -CH = CH ₂ H -NH ₂ 199-201 1:39 H -CH2-CH = CH2 H -nh ₂ 191-193 1:40 H -ch ₂ -c = ch H -nh ₂ -260 1:41 H cyclopropylmethyl H -NH ₂ 228-229 1:42 H cyclopropyl -CO-CH3 -NH-CO-CH 3 > 260 1:43 C2H5 C2H5 -CO-CH3 -NH-CO-CH 3 263-265

The following salts of the compounds of formula I are prepared by reaction with the acids mentioned in the table in a known manner:

Compound number Ltd. RZ R3 R4 Acid Melting point (° C) 2.1 H cyclopropyl H -NH ₂ HC1 210 (during decomposition) 2.2 H cyclopropyl H -nh ₂ F3C-COOH 209-210 2.3 H cyclopropyl H -NH ₂ (COOH) 2 198 (during decomposition) 2.4 C2H5 C2H5 H -NH ₂ HC1 167-169 2.5 C2H5 C2H5 H -nh ₂ F3C-COOH 175-178 2.6 C2H5 C2H5 H -nh ₂ (COOH) 2 178-188 2.7 H cyclopropyl H -NH-CO-CH (CH ₃ ) ₂ HC1 -140 2.8 H cyclopropyl H -NH-CO-CH (CH ₃ ) ₂ CF3COOH 150-153 2.9 H cyclopropyl H NH2 H3PO4 208 2:10 H cyclopropyl H -NH ₂ H2SO4 188 2:11 C2H5 C2H5 H -nh ₂ H2SO4 199-201 2:12 C2H5 C2H5 H -nh ₂ H3PO4 185 2:13 C2H5 C2H5 H -NH ₂ CH3SO3H 205-207 2:14 H cyclopropyl H -nh ₂ CH3SO3H 250 2:15 C2H5 C2H5 H NH2 maleic 150 2:16 H cyclopropyl H -nh ₂ maleic 185 2:17 C2H5 C2H5 H NH2 malonate 216-220 2:18 H cyclopropyl H -nh ₂ HNO3 163 2:19 C2H5 C2H5 H -nh ₂ HNO3 179 2:20 H cyclopropyl H NH2 malonate > 230

The following compounds of formula (I) may also be prepared as described above: R 1 R ₂ R ₃ R 4

H -CII3 H NH2 H C2H5 H -nh ₂ H -C ₃ H ₇ (n) H -nh ₂

-713

HU 201 651 Β

Ri R2 R3 continuation R4 H cyclobutyl H NH2 H cyclopentyl H -NH ₂ H cyclohexyl H -nh ₂ H -CH (C ₂ H ₅ ) 2 H -nh ₂ —C ₃ H ₇ (i) —C ₃ H ₇ (Í) H -NH2 0 OC ₂ H ₅ • 11 / H cyclopropyl H -N = CH-NH-P ^X SC ₃ H ₇ (n) H cyclopropyl H -NH-CO-O-C2H5 C2H5 C2H5 H -NH-CO-O-C2H5 C2H5 C2H5 H -NH-CO-CH2 Cl H cyclopropyl H -NH-CO-C2F5 C2H5 C2H5 H -NH-CO-C2F5 H cyclopropyl H -NH-CO-C ₃ F ₇ (n) C2H5 C2H5 H -NH-CO-C ₃ F ₇ (n) H cyclopropyl -CO-C2H5 -NH-CO-C2H5 H cyclopropyl -CO-C ₃ H ₇ (n) -NH-CO-C ₃ H ₇ (n) H cyclopropyl -CO-CH (CH ₃ ) 2 -NH-CO-CH (CH ₃ ) 2 C2H5 C2H5 -CO-C2H5 -NH-CO-C2H5 C2H5 C2H5 -CO-C ₃ H ₇ (n) -NH-CO-C ₃ H ₇ (n) C2H5 C2H5 -CO-CH (CH ₃ ) 2 -NH-CO-CH (CH ₃ ) ₂ H cyclopropyl -CO-CF 3 -NH-CO-CF 3 C2H5 C2H5 -co-cf ₃ -NH-CO-CF ₃ H cyclopropyl -CO-CH ₃ -NH-CO-CH (CH ₃ ) ₂ C2II5 C2H5 -CO-C2H5 -NH-CO-CH (CH ₃ ) 2

The following intermediates of formula (II) are prepared as described above:

Compound number Ri r ₂ R3 n Melting point (° C) 3.3 H -ch ₃ H 0 270-274 3.4 H -C ₃ H ₇ (i) H 0 171-173 3.5 - (CH ₂ ) 4 - H 0 198-200 3.6 - (CH ₂ ) s - H 0 204-206 3.7 H -C (CH ₃ ) ₃ H 0 194-196 3.8 H -CH (CH ₃ ) -C ₂ H ₅ H 0 143-145 3.9 H -CH (C ₂ H 5) 2 H 0 151-153 3:10 -ch ₃ -ch ₃ H 0 216-218 3:11 C2H5 C2H5 H 0 131 3:12 -ch ₃ C2H5 H 0 158-160 3:13 -ch ₃ -C ₄ H ₉ (n) H 0 158-160 3:14 -C ₃ H ₇ (n) -C ₃ H ₇ (n) H 0 160-162 3:15 -C ₄ H ₉ (n) -C ₄ H ₉ (n) H 0 120-122 3:16 H H H 0 ~ 270 (during decay) 3:17 H cyclopropyl H 2 167-170 3:18 -CH ₃ -CH ₃ H 2 237-239 3:19 -C ₃ H ₇ (n) _C ₃ H ₇ (n) H 2 222-225 3:20 -C ₄ H ₉ (n) _C ₄ H ₉ (n) H 2 165-167 3:21 -CH ₃ C2H5 H 2 203-205 3:22 - (ch / _ H 2 235-237 3:23 - (CH ₂ ) ⁵ H 2 204-207 3:24 -CH ₃ -C ₄ H ₉ (n) H 2 190-191

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HU 201 651 Β

The following intermediates of general formula II may be prepared as described above:

Ri R 2 R ₃ R n R ₂ R ₃ n

H C2H5 H 0 - 5 H -CH ₃ H 2 H -C ₃ H ₇ (n) H 0 H C2H5 H 2 H -C ₃ H ₇ (i) H 0 H -C ₃ H ₇ (n) H 2 H -CH (C ₂ H ₅ ) ₂ H 0 -C ₃ H ₇ (i) -C ₃ H ₇ (i) H 2 H cyclobutyl H 0 10 H cyclobutyl H 2 H cyclopentyl H 0 H cyclopentyl H 2 H cyclohexyl H 0 H cyclohexyl H 2 H -CH (CH ₃ ) -C ₂ H ₅ H 0 H -CH (CH ₃ ) -C ₂ H ₅ H 2 -CH ₃ -ch ₃ H 0 H -CH (C ₂ H _s ) ₂ H 2 -CzHs -c ₂ h ₅ H 0 15

The following intermediates of general formula (XII) are prepared as described above:

Compound number Ri R2 Melting point ('C) 4.1 H -ch ₃ 270-274 4.2 H -C ₃ H ₇ (i) 171-173 4.3 H cyclopropyl 215-218 4.4 H -CH (CH ₃ ) -C ₂ -H 5 143-145 4.5 H -CH (C ₂ H 5) 2 151-153 4.6 CH3 -ch ₃ 216-218 4.7 C2H5 C2H5 131 4.8 -C ₃ H ₇ (n) -C ₃ H ₇ (n) 160-162 4.9 -C ₄ H ₉ (n) -C ₄ H ₉ (n) 120-122 4:10 H H 270 (decomposes) 4:11 -CH ₃ C2H5 158-160 4:12 H -C (CH ₃ ) ₃ 194-196 4:13 - (CH2) 4- 198-200 4:14 ~ (CH ₂ ) 5- 204-206 4:15 -ch ₃ -C ₄ H ₉ (n) 158-160

The following intermediates of formula (XII) may also be prepared as described above:

Ltd. R2 H C2H5 H -C ₃ H ₇ (n) H cyclobutyl H cyclopentyl H cyclohexyl -C ₃ H ₇ (i) -C ₃ H ₇ (i)

Example 6

1-3. Formulations of the active compounds of Examples 1 to 4 or combinations thereof with other insecticidal or acaricidal active ingredients.

In the following examples, the% value represents the percentage by weight.

1. Wettable powder

the) b) c) 1.1-1.43 active ingredients 60 any 25'λ 50% 75% Twice with sodium lignin sulfonate well 5% 5% - Sodium laureth sulfate 3% - 5% Twice with sodium diisobutyl naphthalene sulfonate - 6% 10% 65

Octyl-phenol-poly (ethylene glycol) ether (7-8 moles ethylene oxide) - 2% High dispersion silica 5% 10% 10%

Kaolin 62% 27% The active ingredient or the combination of active ingredients is thoroughly mixed with the additives and triturated in a suitable mill. This gives a wettable powder which can be formulated in water with any desired concentration of suspension.

2. Concentrations of emulsion

1.11.43 Any active ingredient 10%

Octylphenol-poly (ethylene glycol) -ctcr (4-5 moles ethylene oxide) 3%

Ca 2 -Dodcyl 1-Benzenesulfonate 3%

Castor oil polyglycol ether (36 moles ethyl oxide) 4%

Cyclohexanone 30%

Xylene Clcgy 50%

By diluting the above concentrate with water, any desired concentration of emulsion can be prepared.

3. Dusting agent

a) b)

1.1-1.43 any of the active ingredients 5% 8%

95% Talk

Kaolin - 92%

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HU 201 651 Β

A ready-to-use powder can be prepared by mixing the active ingredient or combination of active ingredients with the carrier and grinding it in a suitable mill.

4. Extruded granules

1.1-1.43 any of the active ingredients 10%

Sodium lignin sulphonate 2%

Carboxymethylcellulose 1%

Kaolin 87%

The active ingredient or combination of active ingredients is admixed with the additives, triturated with damp water. The mixture was extruded, granulated and air-dried.

5. Coated granules

1.1-1.43 any of the active ingredients 3%

Polyethylene glycol (Ms = 200) 3%

Kaolin 94%

The finely divided active ingredient or combination of active ingredients is applied uniformly to the kaolin coupled with polycarbonyl glycol mcgncdvc. In this way, a powder-free coated granulate is prepared.

6. Suspension concentrate

1.1-1.43 any of the active ingredients 40%

Ethylene glycol 10%

Nonyl phenol polyethylene glycol ether (15 moles ethylene oxide) 6%

Sodium lignin sulphonate 10%

Carboxymethylcellulose 1%

37% aqueous formaldehyde solution 0.2%

Silicone oil (75% aqueous emulsion) 0.8%

Water 32%

The finely divided active ingredient or combination of active ingredients is intimately mixed with the additives. In this way, a suspension concentrate is obtained which can be diluted with water to form any suspension of the desired concentration.

7. Watering solution ('pour on preparation')

Any of the active ingredients 1.1-1.43 is 30.00 g

Sodium dioctylsulfosuccinate 3.00 g

Gasoline Alcohol 35.46 g

Ethylene glycol monomethyl αcr 35.46 g

103.92 g = 100 mL

The active ingredient is dissolved in most of the two solvent mixtures under vigorous stirring. Sodium dioctylsulfosuccinate dissolved in the remainder of the solvent mixture is then added and optionally heated.

Example 7

Effect against Musca domestica

50-50 g of freshly prepared rabbit broth is added to the dishes. A volume of 1 to 4% solution of the active ingredient 1.1 to 1.43 in acton was added to the culture medium in the dishes so that the concentration of the active ingredient was 800 ppm. After mixing the medium, the acetone is allowed to evaporate for at least 20 hours.

Subsequently, 25-25 day old Musca domcstica calves were placed in the dishes containing the treated medium as active ingredient and concentration. After the stumps have been puppetized, the resulting puppets are separated from the substrate by sliding them in water and placed in closed mesh containers. The puppets that were flushed out per dish were counted (number of toxic activity indicator for rabbit development). After 10 days, the number of flies from the pupae was determined.

1-3. Examples 1.1-1.43 of Examples 1 to 4 showed at least 50-60% activity (mortality).

Example 8

Action against Lucilia sericata 1 ml of an aqueous formulation containing 0.5% by weight of the active ingredient was added dropwise at 50 ° C to the culture side. Thereafter, the culture medium was diluted with ca. 30 freshly puped larvae of Lucilia sericata were added to the tube at 48 hours 96 hours and the insecticidal activity was determined by monitoring the killing value.

1-3. Examples 1.1-1.43 of Examples 1 to 4 show at least 50-60% activity (mortality) against Lucilia scricata.

Example 9

Effect against Lucilia cuprina

Freshly laid eggs of Lucilia cuprina sturgeon were placed in small portions (30-50 eggs) in test tubes previously filled with a mixture of 4 ml of nutrient solution and 1 ml of active ingredient solution. After the medium was inoculated, the tube was sealed with a cotton plug and kept in a 30 C oven for 4 days.

Compared to the untreated medium, approx. 1 cm larvae (stage 3) developed. If the material is effective, the larvae are either dead or non-viable at this time. The experiment was carried out at a concentration of 400 ppm. We also recorded that the larvae had migrated from the nutrient medium and had died of starvation.

1-3. The compounds of Examples 1.1 to 1.43 showed at least 50-60% activity (mortality) against Lucilia cuprina.

Example 10

Effect on Aedes aegypti

An amount of 0.1% w / v acetone in drug solution was pipetted onto 150 ml of water in a container to produce a solution of 800 ppm. The acetone was evaporated and 30-40 2 day old Aedes larvae were placed in the vessel. After one, two and five days, the mortality value is determined.

1-3 in the experiment below. Compounds of formula (I) according to Examples 1 to 4 show at least 50-60% activity (mortality) against Aedes aegypti.

Example 11

Toxic effect by chewing insecticide

Cotton plants sprouted in about 25 cm pots were sprayed with aqueous emulsion containing 100,200 and 400 ppm of active ingredient.

After drying of the meadow, cotton seedlings of Spodoptera liltoralis and Hcliothis virescens were planted in the 3rd larval stage. The experiment was carried out at 24 'C

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HU 201 651 Β and 60% relative ncdvcsscg air. After 2 days,% mortality of larvae was determined.

In the above experiment, 1.1. and 1.2 of the present invention, at concentrations of 200 and 400 ppm respectively, exhibit 80-100% activity (mortality) against Spodoptera larvae. Drug 1.1 at 100 ppm and Drug 1.2 at 400 ppm showed 80-100% mortality against Heliothis larvae.

Example 12

Effect against Anthonomus grandis (adult)

Two potted six-leaf cotton plants were sprayed with an aqueous wettable emulsion formulation containing 400 to 400 ppm of the active ingredient to be tested. After the spray had dried (about 1.5 hours), 10 to 10 adult beetles (Anthonomus grandis) were planted on each plant. A plastic roll was applied to the treated and test animal infected plants, the upper opening of which was covered with a bandage to prevent the migration of the beetles. The plants so treated were maintained at 25 ° C and ca. It was kept in air containing 60% relative ncdvcsscg. Evaluation was carried out at 2,3,4 and 5 days and the% mortality of the animals administered and the control effect was established.

1-3 in the fend assay. Examples 1.1-1.43 of Examples 1 to 4 show at least 50-60% activity (mortality).

Example 13

Effect against tick

A. Amblyoma hebraeum nymphate was placed in a glass tube and immersed in 2 ml of an aqueous emulsion containing 400 ppm of test substance for 1-2 minutes. The tube was then sealed with a cotton wool plug and turned downward with a stopper to absorb the halogen emulsion into the cotton wool.

Evaluation was performed after one week. Each experiment was performed in duplicate in duplicate.

B. Boophilus microplus (larvae)

The same dilution series was used as in assay A above, with 20 to 20 sensitive and OP resistant larvae. (Resistance refers to diazinon tolerance.)

1-3. Examples 1.1-1.43 of Examples 1 to 4 in the fend assay showed at least 50-60% activity (mortality) against nymphs and larvae of Amblyoma hebraeum and Boophilus microplus.

Example 14

Insecticide: Nilaparvata lugens

Rice plants were sprayed with a solution containing 400 ppm of the test compound. After the spray dried, N2 or N3 nymphs of Nilaparvata lugens were placed on the plants. Two plants per test compound and experimental animal were used. Percentage evaluation of the insecticide was performed after 6 days. The experiment was conducted at 26 ° C and 60% RH.

Compound 1.1 in the above assay showed 80-100% activity against Nilaparvata lugens nymphs.

Example 15

Fishing against soil insects (Diabreotica balleata)

Five corn sprouts (1-3 cm) and filter paper discs were immersed in an aqueous solution containing 4 volumes of acetone. The dipped filter paper disk was placed on the bottom of a 200 ml plastic cup and placed on it with a dry tissue paper disk, corn germs and 10 diabrotica baltcata larvae in the second or third larval stage. Evaluation was performed at 6 days relative to untreated controls.

Compound 1.15 of the present invention exhibited an 80100% mortality at 400 ppm in fend studies.

Example 16

Effect against Nephoteltix cincticeps (nymphs)

The experiment was carried out on growing plants. About 20 days old rice plants (about 15 cm high) were planted in pots 5.5 cm in diameter.

Plants were sprayed on a turntable with 100-100 ml of acetone solution containing 400 ppm of test substance. After the spray had dried, 20-20 second or third stage nymphs were planted on each plant. To prevent the migration of cicadas, we planted a plexiglass tube on the planted plants, covered with bandage. The nymphs were kept on the treated plants for 5 days and watered at least once. The experiment was carried out for approx. It was performed at 23 'C, 55% RH and 16 hours of daylight.

Compound 1.1 showed 80-100% activity in the above experiment.

Example 17

Insecticidal chewing toxicity against Plutella xylostella

Four-leaf cauliflower plants planted in pots (10 cm in diameter) were sprayed with an aqueous emulsion containing 300-400 ppm of active ingredient and the plants were dried.

Two days after treatment, 10 to 10 larvae of Plutella xylostella were planted on the plants. Evaluation was performed on days 2 and 5, during which the larval mortality rate was determined. The experiment was performed at 24 'C and 60% RH.

1-3. The compounds of formula (I) according to Examples 1 to 9 showed 80-100% mortality in the above assay.

Claims (9)

A process for the preparation of a compound of formula (I) R! hydrogen or C 1-6 alkyl, R _{2 is} hydrogen, C 1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl or C2-6 alkynyl, or Ri and _R2 together form a (CHiX- or - (the radical CHJy-, -1 121 HU 201 651 Β R _{3 is} hydrogen or a group -CO-R ₅ , _R4 is _a-NH2, -NH-CO-R _s, -N = CN 'or -NH-CH = NR ₁₀ R is R _and C 1-10 alkyl or C 1-3 perhalogenated alkyl group, R _{7 is} hydrogen, R _e and R ₉ are each independently hydrogen or C 1-6 alkyl, R 10 is -SO ₂ -C 0-4 alkyl) or X O-R " HX -P \, Y-R R _w and R ₁₃ are each independently C 1 -C 5 alkyl, X and Y are each independently oxygen or sulfur, and salts thereof, characterized in that: a) a compound of formula II is ammonia; (b) reacting a compound of formula (III) with a compound of formula (IV) and the resulting compound of formula (I) wherein R _{3 is} hydrogen and R _{4 is} -NH ₂ , optionally in a manner known per se; wherein R ₃ is -CO-R ₅ and / or R ₄ -NH-CO-R, R ₇ Aug I / 40 -N = CN or -NH-CH = NR ₁₀ R 1, wherein R 1, R 2, R 3, R 6, R 8, R 7, R 7, R 8, R 10, R 10, R 14, R 15 X and Y are as defined above, and n is an integer of 0, 1 or 2 and optionally converting the resulting compound of formula I into a salt thereof. 50 A process according to claim 1 for the preparation of a compound of formula (I) or a salt thereof, wherein: R, hydrogen or C 1-4 alkyl, R _{2 is C} 1-4 alkyl or C 3-6 cycloalkyl, or R 1 and R ₂ together form a - (CH ₂ - or - (CH ₂ ) _{5 -} group, R _{3 is} hydrogen, Rt is -NH ₂ or -NH-CO-R j and R _{5 is C} 1 -C 4 alkyl or perhalogenated C 1 -C 3 alkyl, characterized in that it is substituted with an appropriately substituted compound. 3. A process according to claim 2 for the preparation of compounds of formula (I) and salts thereof R1 is hydrogen, methyl or ethyl, R _{2 is C} 1-4 alkyl or cyclopropyl, R _{3 is} hydrogen, R _{4 is} -NH ₂ or -NH-CO-R _S , and C 1-3 alkyl is characterized in that it is derived from appropriately substituted compounds. A process according to claim 3 for the preparation of a compound of formula (I) or a salt thereof, wherein: Rj is hydrogen, methyl or ethyl, R _{2 is} cyclopropyl, R _{3 is} hydrogen; and R ₄ is -NH ₂ or -NH-CO-C ₂ H ₅ , characterized in that it is derived from appropriately substituted compounds. A process for the preparation of a compound of formula (XVI) according to claim 4, characterized in that it is based on appropriately substituted compounds. A process for the preparation of a compound of formula (XVIII) according to claim 4, characterized in that it is based on the appropriately substituted compounds. The process for the preparation of the compound of formula (XXI) according to claim 4, characterized in that it is based on appropriately substituted compounds. A process for the preparation of a compound of formula (XXII) according to claim 4, characterized in that it is based on the appropriately substituted compounds An insecticidal and acaricidal composition, characterized in that the active ingredient is 0.01 to 95% by weight of a compound of the formula I as claimed in claim 1, wherein _{Rb R2, R3} and _R4 are as defined in claim 1, defined above, or a salt of these compounds, from 0.01 to 95% by weight of a solid or liquid carrier or additive and 0 to 25%, by weight, in particular from 0.1 to 20 parts by weight % with tenside.